Sodium Butyrate leads to weight loss and less inflammation/endotoxin

[Adf]

Frozen potatoes. They have to be blanched before freezing so this creates resistant starch in them apparently since heat -> cool -> resistant starch. My dog is getting them too and his digestion is improving as well lol

Do you know if the potatoes have to be frozen?

Say you made mashed potatoes, or potato bake from room temperature potatoes, then store it in the refrigerator, and reheat later, would that form some resistant starches too?

 

[DrJ]

Do you know if the potatoes have to be frozen?

Say you made mashed potatoes, or potato bake from room temperature potatoes, then store it in the refrigerator, and reheat later, would that form some resistant starches too?

No definitely not. I just find frozen ones cheap and convenient. As I understand it you only need to cool the potatoes after cooking them for resistant starch to form. Therefore, by putting cooked potatoes in the refrigerator, you should produce resistant starch, even if you heat them back up. At some point I found a site that listed how many grams of resistant starch you would generally get from a potato by cooling it, but I seem to have misplaced it

 

[PeskyPeater]

Frozen potatoes. They have to be blanched before freezing so this creates resistant starch in them apparently since heat -> cool -> resistant starch. My dog is getting them too and his digestion is improving as well lol

increasing resistant starch will increase SCFA which increase serotonin that can improve bowel movement.

“Bacterial endotoxin increases serotonin release from the intestine, and increases its synthesis in the brain (Nolan, et al., 2000) and liver (Bado, 1983). It also stimulates its release from platelets, and reduces the lungs’ ability to destroy it. The formation of serotonin in the intestine is also stimulated by the lactate, propionate and butyrate that are formed by bacteria fermenting fiber and starch, but these bacteria also produce endotoxin. The inflammation-producing effects of lactate, serotonin, and endotoxin are overlapping, additive, and sometimes synergistic, along with histamine, nitric oxide, bradykinin, and the cytokines.” RP

 

[Perry Staltic]

oh and SCFA in turn increase endotoxin.

Not all do and not all LPS are bad. If the intestinal barrier is good there's nothing to worry about because the bad LPS get flushed out

 

[PeskyPeater]

Not all do and not all LPS are bad. If the intestinal barrier is good there's nothing to worry about because the bad LPS get flushed out

Im sorry my mistake. It is of course the gram negative germs that have endotoxins not the SCFA hehe

 

[Mauritio]

Here's another very interesting study on butyrate.
Mice fed a high fed diet + butyrate weighed about half of HDF-mice and had just 1/3 of their body fat.

They simply burned the excess calories off ,as seen in increases in energy expenditure, UCP1 and PGC1a.

Butyrate improves insulin sensitivity and increases energy expenditure in mice - PubMed

Dietary supplementation of butyrate can prevent and treat diet-induced insulin resistance in mouse. The mechanism of butyrate action is related to promotion of energy expenditure and induction of mitochondria function.

pubmed.ncbi.nlm.nih.gov

 

[PeskyPeater]

Dr Peat mentioned overlapping effects of the SCFA from the gut microbes and endotoxin:

“Bacterial endotoxin increases serotonin release from the intestine, and increases its synthesis in the brain (Nolan, et al., 2000) and liver (Bado, 1983). It also stimulates its release from platelets, and reduces the lungs’ ability to destroy it. The formation of serotonin in the intestine is also stimulated by the lactate, propionate and butyrate that are formed by bacteria fermenting fiber and starch, but these bacteria also produce endotoxin. The inflammation-producing effects of lactate, serotonin, and endotoxin are overlapping, additive, and sometimes synergistic, along with histamine, nitric oxide, bradykinin, and the cytokines.”

Here is a thesis about Butyrate on the release of serotonin and dopamine. I quotes the serotonin parts:

University of Eastern Finland, Faculty of Health Sciences
School of Medicine Institute of Public Health and Clinical Nutrition
Schubert, Sofie M M:

The effect of oral butyrate administration on the release of serotonin and dopamine in the gastrointestinal tract

Thesis, 64 pages

Supervisors: Professor Marjukka Kolehmainen, Professor Riitta Korpela, Doctor Richard Forsgård 08 2021

Keywords: Butyrate, serotonin, dopamine, gastrointestinal tract

THE EFFECT OF ORAL BUTYRATE ADMINISTRATION ON THE RELEASE OF SEROTONIN AND DOPAMINE IN THE GASTROINTESTINAL TRACT
The microbiota-gut-brain axis is a modern concept with wide and physiologically important effects. The aim of the study was to investigate if an orally given short chain fatty acid (SCFA), butyrate, stimulates the formation and release of serotonin and dopamine in an in vivo rat model. The effect of butyrate was investigated in the entire gastrointestinal tract since previous studies have mainly focused on the colon. A total of seven male Wistar rats (270-300 g) had free access to a 40 mM butyrate solution as the only drink for 10 days while another seven rats had access only to tap water (control group). Urine samples were collected in metabolic cages for 24 h twice during the experiment, once before administration of butyrate and once after 9 days. A section of 5 mm was isolated from the middle of the stomach, duodenum, jejunum, ileum and colon. The sections were homogenized, and the levels of serotonin were assayed using a commercial ELISA kit. The excreted amounts of 5-HIAA and HVA in the urine were assayed using commercial ELISA kits as indicators for serotonin and dopamine respectively. This study showed that butyrate tends to increase duodenal tissue levels of serotonin and decrease serotonin concentrations in the ileum and colon. Butyrate did not affect urinary concentrations of 5-HIAA but appeared to increase the urinary excretion of HVA after 10 days. This finding is important due to the scarce number of studies investigating the effect of butyrate on dopamine. The study suggests that butyrate may influence neurotransmitter concentrations in the gastrointestinal tract and probably in the whole organism. In the future, this might be of importance in understanding and preventing disorders related to the microbiota-gut-brain axis.

3.5.5 Is butyrate able to stimulate the release of serotonin?
In vitro studies have shown that sodium butyrate (0.5 mM and 1 mM) significantly increases the expression of TPH1 mRNA in BON cells, a human enterochromaffin cell model (Reigstad et al. 2015). However, higher levels of sodium butyrate (8 mM and 16 mM) tend to supress the transcription of TPH1. In a similar way, butyrate increases the expression of TPH1 in RIN14B cells, a pancreatic deltacell line (Yano et al. 2015). The increase in TPH1 expression was associated with elevated serotonin levels in the RIN14B cell culture. The mechanism behind butyrate increasing TPH1 expression is believed to be its histone deacetylase inhibitory feature that facilitates gene expression by opening up the chromatin structure (Nankova et al. 2014, Soret et al. 2010). The receptor FFA2 has been detected in enterochromaffin cells in the rat duodenum (Akiba et al. 2015) and both FFA2 and FFA3 have been detected in enterochromaffin cells in the mouse duodenum and colon (Martin et al. 2017b). In contrast to all this, Martin et al. (2017a) showed that butyrate (1-30mM) is not able to acutely stimulate the release of serotonin from isolated mouse duodenal and colonic enterochromaffin cells.

Ex vivo studies have shown that luminal perfusion of a mixture of SCFA (100-200 mM) causes a significant increase in serotonin concentration in the rat colon ex vivo (Fukumoto et al. 2003). The mixture consisted of acetic acid, propionic acid and butyric acid in the molar ratio 65:20:15. Reigstad et al. 2015 showed in a similar way, that a mixture of acetate, propionate and butyrate increases the release of serotonin from a three-compartment flat-sheet preparation of the rat colon. The concentration of the SCFA mixture was 0.5-100 mM.

In vivo studies have shown that healthy adults have a decreased plasma serotonin level after intake of whole grain rye bread compared with intake of refined wheat bread (Keski-Rahkonen et al. 2019). The concentration of plasma SCFA did, however, not differ significantly between the diets, despite differences in the intake of fiber. Keski-Rahkonen et al. 2019 showed that intake of wheat aleurone and rye bran decreases the serotonin level in the jejunum and colon of mice. The mice were fed a high-fat diet supplemented with ground wheat aleurone, rye bran flour or powdered cellulose. Kundi et al. (2021) showed in line with the previous study, that mice fed a western diet have significantly increased ileal TPH1 mRNA-expression, while intake of rye and oat fibres reduce the expression. They showed, moreover, that a western diet significantly reduces the concentration of SCFA, while the concentration is restored by intake of rye or oat fibres. An increased expression of TPH1 was inversely associated with the SCFA concentration.

 

[PeskyPeater]

And here is the Discussion, and limitations further on down, I have not read it yet. Also interesting. let's see what it says:

7.1 General discussion


The aim of the study was to investigate if an orally given SCFA, butyrate, stimulates the formation
and release of serotonin and dopamine from different parts of the gastrointestinal tract in an in vivo
rat model. These questions are of interest, due to the scarcity of in vivo investigations on the effects
of butyrate in the entire gastrointestinal tract. The study showed that the effect of butyrate on tissue
concentration of serotonin varies in different segments of the gastrointestinal tract. Butyrate tends to
increase the tissue level of serotonin in the duodenum but decrease the level of serotonin in the
ileum and colon. The differences were, however, not statistically significant. An important finding was
that the basal production of serotonin appears to be high in the stomach, duodenum and jejunum,
compared to the lower concentrations in the ileum and colon. This study showed that a 40 mM
butyrate solution is not able to affect the urinary excretion of 5-HIAA, the main stable metabolite of
serotonin. However, there was a clear tendency of butyrate to increase the urinary excretion of HVA,
the main stable metabolite of dopamine. This is an important finding since the scarce in vivo
investigations on the effect of butyrate on dopamine. Furthermore, the study showed that a 40 mM
butyrate solution has no negative effect on the rats’ general well-being. Butyrate did not affect the
animals’ food intake, total energy intake nor the body weight gain during 10 days.


There are conflicting results regarding the effect of butyrate on the release of serotonin. In vitro
investigations have shown that sodium butyrate (0.5 mM and 1 mM) significantly increases the
expression of TPH1 mRNA in BON cells, a human enterochromaffin cell model (Reigstad et al. 2015).
However, higher levels of sodium butyrate (8 mM and 16 mM) tend to supress the transcription of
TPH1. Moreover, Martin et al. (2017) showed that butyrate (1-30 mM) is not able to acutely stimulate
the release of serotonin from isolated mouse duodenal and colonic enterochromaffin cells. Ex vivo
investigations have shown that luminal perfusion of a mixture of SCFA (100-200 mM) causes a
significant increase in serotonin concentration in the rat colon (Fukumoto et al. 2003). In a similar
way, Grider and Piland (2007) showed that a mixture of SCFA with concentrations of 0.5-100 mM
increases the release of serotonin from a three-compartment flat-sheet preparation of the rat colon.
In vivo investigations, however, show that healthy adults have a decreased plasma serotonin level
after intake of whole grain rye bread compared with intake of refined wheat bread (Keski-Rahkonen
et al. 2019). Keski-Rahkonen et al. (2019) showed, moreover, that intake of wheat aleurone and rye
bran decreases the serotonin level in the jejunum and colon of mice. Kundi et al. (2021) showed in
line with the previous study, that mice fed a western diet have significantly increased ileal TPH1
mRNA-expression, while intake of rye and oat fibres reduce the expression. Thus, an increased
expression of TPH1 was inversely associated with the SCFA concentration.


This study supports the theory of butyrate decreasing the level of serotonin in the colon. In line with
previous in vivo investigations (Keski-Rahkonen et al. 2019, Kundi et al. 2021), we showed that 40
mM butyrate administered in the drinking water for 10 d decreases the level of serotonin in the rat
colon. Our results are also in line with the in vitro investigations by Martin et al. (2017) and Reigstad
et al. (2015). The butyrate concentration used in the in vitro investigations was lower than 40 mM,
but instead directly applied on the isolated cells. Our results are, however, in contrast with the ex
vivo investigations by Fukumoto et al. (2003) and Grider and Piland (2007). Fukumoto et al. (2003)
showed an increase in the serotonin concentration in the rat colon after luminal perfusion of a
mixture of SCFA (100-200 mM). The mixture consisted of acetic acid, propionic acid and butyric acid
in the molar ratio 65:20:15, which means a butyrate concentration of 15 mM-30 mM. Likewise, Grider
and Piland (2007) showed that a mixture of SCFA with concentrations of 0.5-100 mM increases the
release of serotonin from the rat colon. This contrast might be due to differences in the methods
used as well as the quality of SCFA. We used an in vivo rat model and administered only butyrate. In
the in vivo model butyrate was probably partly absorbed by gastrointestinal cells already in the
duodenum and used as an energy source especially by colonocytes. This would lead to a lower
butyrate concentration than 40 mM reaching the colon. In our in vivo model was also the vasculature
present and able to transport away some of the serotonin released. This is important to take into
account as we analysed the tissue level of serotonin in the colon. Serotonin is primarily released by
exocytosis from the basal membrane into small blood vessels and the lamina propria (Szeitz and
Bandiera 2018). Only a small amount of serotonin is releases from the apical membrane of the
enterochromaffin cells.


This study showed that butyrate tends to increase the level of serotonin in the duodenum. Duodenum
is abundant with receptors FFA2 and FFA3 for butyrate, on the enterochromaffin cells. Butyrate
activates the receptors upon binding, and stimulates the production and release of serotonin. This
might have led to the increased serotonin level in the duodenum, compared to the other parts of the
gastrointestinal tract. The result is, however, in contrast to the in vitro study by Martin et al. (2017)
that showed that butyrate is not able to acutely stimulate the release of serotonin from isolated
mouse duodenal enterochromaffin cells. This contrast might be due to differences in the methods
used as well as differences in the concentration of butyrate used.


We showed a clear tendency of butyrate to increase the urinary excretion of HVA, the main stable
metabolite of dopamine. The result is in line with previous studies: Nankova et al. (2014) showed that
butyrate (1 mM) activates transcription of the TH gene in PC12 cells. Laurent et al. (2013) showed
that sodium butyrate (10 mM) increases the dopamine level in the brain of an alpha-synuclein
Drosophila transgenic model of familial Parkinson’s disease. Furthermore, Hou et al. (2021) showed
that orally given butyrate reaches the brain in a mice model of Parkinson’s disease and increases the
level of TH. The effect of butyrate on dopamine is an interesting field, since the scarce number of
investigations on the topic.

7.2 Limitations
The in vivo study possessed certain limitations that should be considered when interpreting the
results. The most significant are the small number of animals and quite large interindividual
variations. These might explain why the results showed only trends and did not reach statistical
significance. The interindividual variations can be seen already in the baseline sample, and seem to
be naturally occurring, since there was no difference in the amount of consumed butyrate solution or
consumed tap water between the two study groups.
In this study we chose to analyze only the serotonin metabolite 5-HIAA from the urine and not 5-
HTOL. 5-HIAA is shown to effectively reflect the amount of serotonin, but in rats 5-HTOL still make
up 35% of the excreted metabolites (Some and Helander 2002). The 5-HIAA results show, therefor,
an underestimation of total serotonin. Likewise, we chose to analyze HVA as the only dopamine
metabolite, since HVA is the main metabolite produced in the dopamine metabolism (Elsworth and
Roth 1997). There are, however, many other metabolites of dopamine and our result shows an
underestimation of total dopamine. The amount and concentration of urine could have been affected
by the use of metabolic cages. The rats reacted negatively to the new environment, which affected
the amount of consumed liquid and excreted urine individually.

edit - last part:

A time period of 10 d was used in this study. According to the literature, varied time periods have been used, for example Hou et al (2021) used a time period of six weeks. The length of the treatment period used might affect the result, and long-term effects of butyrate should not be concluded from this study. We used a rat model to study the effect of butyrate on serotonin and dopamine. The results can, therefore, not be directly applied on humans. There are physiological differences between the rat gastrointestinal tract and the human gastrointestinal tract, as well as, differences in the composition of gut microbiota.

 

[DrJ]

increasing resistant starch will increase SCFA which increase serotonin that can improve bowel movement.

I think the SCFAs are used as fuel by the enterocytes which I believe is a good thing. Not sure I fully follow the connection you're making with endotoxin.

 

[Vinny]

No, but cooling it (or cooling and reheating) creates resistant starch which feeds butyrate producing bacteria

Cooked and frozen potato croquettes from the grocery - have they got the resistant schmooky-pooky starch?
Thanks

 

[PeskyPeater]

I think the SCFAs are used as fuel by the enterocytes which I believe is a good thing. Not sure I fully follow the connection you're making with endotoxin.

correct, I suppose in the cases for IBS or crohn's there is too little serotonin in the gut cells. Then increasing SCFA may have good effects, but it seems to indicate a disturbance or shift in the population of gut microbes.

 

[PeskyPeater]

... To support my point, I will quote here the last part of that thesis :

7.3 Clinical aspects

7.3.1 Gastrointestinal disorders

Serotonin is an important signaling molecule in the gastrointestinal tract and impairments in the serotonergic signaling appear in ulcerative colitis, Crohn’s disease and IBS (Coates et al. 2004, Ghia et al. 2009, Lou et al. 2021, Magro et al. 2002). Rectal biopsies from patients suffering from ulcerative colitis or IBS contain reduced levels of mucosal serotonin and TPH1 mRNA (Coates et al. 2004). Likewise, serotonin levels are also reduced in the colonic mucosa from patients suffering from Crohn’s disease or ulcerative colitis (Magro et al 2002). Ghia et al. (2009) showed, however, that serotonin plays a central role in the pathogenesis of inflammation in experimental ulcerative colitis in mice and Lou et al. (2021) showed that serotonin might play a role also in the pathogenesis of IBS. Lou et al. (2021) found elevated serotonin levels in blood from patients suffering from IBS compared to healthy controls. If further studies confirm the pathogenic effect of serotonin in gastrointestinal disorders, SCFA might have a potential clinical relevance in the future. In this study, we showed that butyrate tends to decrease the level of serotonin in the colon, a central target for gastrointestinal disorders. It is, however, important to consider the different effects of butyrate in different parts of the gastrointestinal tract.

The gastrointestinal tract is a central source of peripheral dopamine and impairments in the dopaminergic signaling are also related to the development of ulcerative colitis and Crohn’s disease (Liu et al. 2021, Magro et al. 2002). Magro et al. (2002) showed that dopamine levels in the colonic mucosa of patients suffering from ulcerative colitis or Crohn’s disease are significantly lower than in healthy controls. Liu et al. (2021) showed that dopaminergic signaling via the receptor D5 inhibits the development of ulcerative colitis by regulating the ratio of M1/M2 colonic macrophages. If further studies confirm the importance of the dopaminergic signaling in the gastrointestinal tract, dopamine might be a target for prevention of gastrointestinal disorders in the future. If so, also SCFA might have a potential clinical relevance, since this study showed that butyrate tends to increase the level of peripheral dopamine.

 

[shine]

Besides T3, I have not found/tried anything else that increases metabolism like sodium butyrate does.

 

[Perry Staltic]

Cooked and frozen potato croquettes from the grocery - have they got the resistant schmooky-pooky starch?
Thanks

I don't see why not

 

[Mauritio]

Besides T3, I have not found/tried anything else that increases metabolism like sodium butyrate does.

Interesting. Can you expand on that?

I personally noticed that I'm sweating more easily and feel warmer.
As can be seen in the studies butyrate increases uncoupling, heat production and CO2.

 

[Coderr]

Why is everyone talking about potatoes for butyrate production? Wouldn't pasta be easier for this? Also more delicious. Or less butyrate from pasta?

 

[miquelangeles]

Interesting. Can you expand on that?

I personally noticed that I'm sweating more easily and feel warmer.
As can be seen in the studies butyrate increases uncoupling, heat production and CO2.

I get the same metabolic boost from inulin, which ferments into butyrate and acetate.
I found myself opening the windows last winter in sub zero temperatures. I rarely supplement it though, because it has been linked to liver cancer in animal studies.

 

[Korven]

Why is everyone talking about potatoes for butyrate production? Wouldn't pasta be easier for this? Also more delicious. Or less butyrate from pasta?

Yeah any cooked and cooled starch will have resistant starch. And green bananas (uncooked).

 

[Perry Staltic]

I get the same metabolic boost from inulin, which ferments into butyrate and acetate.
I found myself opening the windows last winter in sub zero temperatures. I rarely supplement it though, because it has been linked to liver cancer in animal studies.

8 Foods High in Inulin You Should Be Eating for Better Gut Health | Livestrong.com

Foods high in inulin fiber are all plant-based and include chicory root, garlic, bananas, leeks, Jerusalem artichokes and more for good gut health.

www.livestrong.com

 

[Mauritio]

Here's a good review on the pros and cons of butyrate.
Showing effects are concentration dependent.
Also shows that the in-vitro studies don't apply, because they don't factor in butyrate consumption by gut cells.

"Butyrate promotes intestinal barrier function at low concentrations (≤2 mM) (77) but may disrupt intestinal barrier function by inducing apoptosis at high concentrations (5 or 8 mM) (79). On the basis of the physiologic concentration in mammalian gastrointestinal tract, the recommended concentration of butyrate used in in vitro models is currently 0–8 mM (80). However, considering that the majority of butyrate is metabolized as energy substrate by the colonic epithelium (12), the dosages used for treatment may be quite different between in vivo and in vitro models (4). For example, a dose of 100 mM butyrate by rectal administration was commonly used in clinical practice, which is comparable with physiologic concentrations in the colon of humans after the consumption of a high-fiber diet (81)."


"Through FA oxidation, colonic cells exhibit a great capacity to rapidly oxidize butyrate into carbon dioxide (111)."

Butyrate: A Double-Edged Sword for Health?

Butyrate, a four-carbon short-chain fatty acid, is produced through microbial fermentation of dietary fibers in the lower intestinal tract. Endogenous butyrate production, delivery, and absorption by colonocytes have been well documented. Butyrate exerts ...

www.ncbi.nlm.nih.gov